{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:19:46Z","timestamp":1790734786679,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2316,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium\u2013glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type\u20092 diabetes, many of whom were retrospectively identified as having HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>The EMPEROR-Preserved Trial is enrolling \u22485750 patients with HFpEF (ejection fraction &amp;gt;40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg\/day, which is added to all appropriate treatments for HFpEF and co-morbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study aims<\/jats:title>\n                    <jats:p>The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death,<\/jats:p>\n                    <jats:p>all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1596","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T03:58:05Z","timestamp":1568606285000},"page":"1279-1287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":222,"title":["Evaluation of the Effects of Sodium\u2013Glucose Co-Transporter 2 Inhibition with Empagliflozin on Morbidity and Mortality in Patients with Chronic Heart Failure and a Preserved Ejection Fraction: Rationale for and Design of the EMPEROR-Preserved Trial"],"prefix":"10.1093","volume":"21","author":[{"given":"Stefan D.","family":"Anker","sequence":"first","affiliation":[{"name":"Department of Cardiology (CVK) and Berlin Institute of Health Centre for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"University of Mississippi School of Medicine , Jackson, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerasimos S.","family":"Filippatos","sequence":"additional","affiliation":[{"name":"School of Medicine, National and Kapodistrian University of Athens, Athens University Hospital Attikon , Athens ,","place":["Greece"]},{"name":"School of Medicine, University of Cyprus , Nicosia ,","place":["Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waheed","family":"Jamal","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Salsali","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Schnee","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc. , Ridgefield, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kimura","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Canada Ltd , Burlington, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Zeller","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothis","family":"George","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Brueckmann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH , Ingelheim ,","place":["Germany"]},{"name":"Faculty of Medicine Mannheim, University of Heidelberg , Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Inserm INI-CRCT, CHRU, University of Lorraine , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , Dallas, TX ,","place":["USA"]},{"name":"Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"2026011721321150700_ejhf1596-bib-0001","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1002\/ejhf.1183","article-title":"Are the effects of drugs to prevent and to treat heart failure always concordant? 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